Is DAZAP2 p.Pro73Leu (c.218C>T) pathogenic?

DAZAP2 p.Pro73Leu (c.218C>T) is classified Uncertain significance in DAZAP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-12). AlphaMissense: likely pathogenic (0.9848); Absent from gnomAD v4.1.

How common is DAZAP2 p.Pro73Leu (c.218C>T) in the general population?

DAZAP2 p.Pro73Leu (c.218C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DAZAP2 p.Pro73Leu (c.218C>T)?

AlphaMissense predicts likely pathogenic (score 0.9848) — an in-silico prediction, not a clinical call.

DAZAP2 p.Pro73Leu

c.218C>T · VCV4009446

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9848 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9848	likely pathogenic · top 6% in DAZAP2
REVEL	0.48	indeterminate
SaProt	LLR -12.57	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.4, phastCons 1
Regional constraint	o/e 0.80	unconstrained · MANE · 3,547 bp · p 0.0028 · regional, not allelic
Overall
CADD	27.8	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: DAZAP2
Protein: p.Pro73Leu
Coding: c.218C>T
MANE Select: NM_014764
Type: single nucleotide variant
Location: chr12:51240956 (GRCh38)
Gene constraint: LOEUF 0.457 · pLI 0.98 (gnomAD)
Structure: AlphaFold pLDDT 58.37

Full DAZAP2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

SMAGP p.Glu73Ala Uncertain significance ★ ⚠ same residue
DAZAP2 c.*118G>A Uncertain significance ★ same type
DAZAP2 c.*24G>A Uncertain significance ★ same type
DAZAP2 c.*50C>G Uncertain significance ★ same type
DAZAP2 c.*51T>G Uncertain significance ★ same type
DAZAP2 c.*58A>G Uncertain significance ★ same type
DAZAP2 c.*5C>G Uncertain significance ★ same type
DAZAP2 p.Ala79Thr Uncertain significance ★ ⚠ same type

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/dazap2-p-pro73leu (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown